沙苑子总黄酮对内质网应激诱导的细胞凋亡在百草枯致大鼠肺损伤中的保护作用

发布时间：2018-02-04 20:09

本文关键词： 百草枯肺损伤细胞凋亡内质网应激沙苑子总黄酮　出处：《医学研究生学报》2014年08期 　论文类型：期刊论文

【摘要】：目的肺组织是百草枯中毒后主要损伤的靶器官,但其具体机制目前尚未完全清楚。内质网应激(endoplasmic reticulum stress,ERS)与中毒相关性疾病密切相关,但其与百草枯中毒后肺损伤的关系鲜见报道。文中探讨ERS诱导的细胞凋亡在大鼠百草枯中毒后急性肺损伤(acute lung injury,ALI)中的作用及观察中药沙苑子黄酮(total flavonoids from astragalus complanatus,FAC)对其影响。方法 30只Spragne-Dawley(SD)大鼠按随机数字表法分为对照组、肺损伤模型组(ALI组)和沙苑子黄酮处理组(ALI+FAC组)。采用生物化学法检测肺组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA)含量;采用原位末端标记(TUNEL)法观察肺组织凋亡情况;采用Western blot及RT-PCR检测ALI后CCAAT增强子结合蛋白(C/EBP)同源蛋白(C/EBP homologous protein,CHOP)、活化的转录因子4(activating transcription factor 4,ATF4)和X-盒结合蛋白-1(X-box binding protein 1,XBP1)基因表达的改变;HE染色观察肺组织病理变化。结果与对照组相比,ALI组的肺组织中MDA水平明显升高[(3.26±0.24)vs(5.04±0.36),P0.01],SOD和CAT活性明显降低,分别为[(300.26±35.69)vs(187.21±25.66)]、[(5.78±1.28)vs(2.15±1.12),P0.01],细胞凋亡数增多,CHOP蛋白表达上调[(0.74±0.20)vs(0.23±0.07),P0.01],XBP-1、ATF4和CHOP mRNA表达水平明显上调。而沙苑子黄酮作用后,肺组织MDA含量减少[(5.04±0.36)vs(3.99±0.27),P0.01],SOD和CAT活性增加,细胞凋亡明显减少,CHOP蛋白表达下调[(0.74±0.20)vs(0.42±0.11),P0.01],ATF4、XBP1和CHOP基因表达下调。结论内质网应激诱导的细胞凋亡参与百草枯中毒后肺损伤过程,沙苑子黄酮对百草枯中毒后肺组织保护作用与其减轻ERS诱导的细胞凋亡有关。
[Abstract]:Objective Pulmonary tissue is the main target organ after paraquat poisoning. However, the specific mechanism of endoplasmic reticulum stress (ER) is not completely clear. Endoplasmic reticulum stress (ER) is closely related to poisoning related diseases. However, the relationship between ERS and lung injury after paraquat poisoning was rarely reported. The aim of this study was to investigate the role of ERS induced apoptosis in acute lung injury induced by paraquat poisoning in rats. The role and observation of total flavonoids from astragalus complanatus in Astragalus complanatus L. Methods Thirty Spragne-Dawley SD rats were randomly divided into control group. Lung injury model group (Ali group) and Astragalus complanatus flavonoids treatment group (Ali FAC group). The lung tissue superoxide dismutase (SOD) was detected by biochemical method. Catalase catalase (CAT) and malondialdehyde (MDA) content; Tunel was used to observe the apoptosis of lung tissue. Western blot and RT-PCR were used to detect CCAAT enhancer binding protein C / EBP homologous protein (. C/EBP homologous protein. Chopo, an activated transcription factor 4, activates transcription factor 4. ATF4) and X-box binding protein 1 (XBP1) gene expression; The pathological changes of lung tissue were observed by HE staining. Results compared with the control group, the level of MDA in lung tissue of Ali group was significantly higher than that of control group. [The activities of sod and CAT were significantly decreased (5.04 卤0.36, P0.01), respectively (P < 0.05). [300.26 卤35.69 vs 187.21 卤25.66). [The number of apoptosis increased and the expression of chop protein was up-regulated. [XBP-1 was found in 0.74 卤0.20 卤0.20 卤0.23 卤0.07 (P0.01). The expression of ATF4 and CHOP mRNA was upregulated obviously, while the content of MDA in lung tissue decreased after flavonoids of Astragalus complanatus were treated. [The activities of sod and CAT increased, and apoptosis decreased significantly. The expression of chop protein was down-regulated. [ATF4 was found in 0.74 卤0.20 卤0.20 卤0.42 卤0.11 (P0.01). Conclusion the apoptosis induced by endoplasmic reticulum stress is involved in the lung injury after paraquat poisoning. The protective effect of flavonoids from Astragalus complanatus on the lung tissue after paraquat poisoning was related to the reduction of apoptosis induced by ERS.
【作者单位】：重庆市巴南区人民医院ICU;
【基金】：重庆市卫生局医学科研计划项目(2012-2-419)
【分类号】：R563.8
【正文快照】： 0引言作为农业生产中常用的除草剂,百草枯自问世以来中毒事件屡有发生。肺是百草枯作用于机体最主要的靶器官,肺损伤是百草枯中毒后最常见的致死原因。目前认为百草枯中毒后氧化应激是肺损伤的主要机制之一,而内质网对氧化应激非常敏感,当其稳态被打乱后将导致内质网应激(endo

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